This revision expands the focus of the OAIC to "mitochondrial function and fatigue". Fatigue is a major complaint among older adults and is strongly associated with loss of independence and impairments regardless of underlying medical conditions. Multiple biological and psychosocial factors may contribute to or influence fatigue. In particular, skeletal muscle mitochondrial dysfunction can lead to reduced energy production, which could result in fatigue. The new focus on mitochondrial function and fatigue will complement and enhance the sarcopenia theme of the parent grant. To address this new focus we propose the revision of three OAIC cores with the addition of new assessments and a new pilot study. The Clinical Research Core will include oxygen consumption measures to assess whole body energy efficiency and utilization (V02peak), in vivo MRI assessments of mitochondrial function, activity monitoring, and comprehensive health and psychosocial assessments of fatigue to characterize the phenotype of fatigue. The Genomics, Metabolism and Biomarkers Core will provide the following novel technologies: (a) intravital multiphoton excitation laser-scanning microscopy to obtain assessments of mitochondrial function, and iron (Fe) accumulation and localization, (b) high-resolution respirometry to assess mitochondrial respiration, and electron transport chain and OXPHOS capacity in situ, (c) Blue native gel electrophoresis (BN PAGE) to determine content and enzymatic activity of the individual mitochondrial respiratory complexes, and (d) array-based genomic analysis to identify genotypic and phenotypic differences correlated with muscle mitochondrial function and iron (Fe) homeostasis, utilizing genome-wide association studies and exon expression analysis. The Biostatistics and Data Management Core will implement bioinformatics and analyses of genomic data. Economic impact The University of Florida (UF) contributes substantially to the local and regional economy. In 2008, UF created 2,525 jobs and recent studies have shown that UF contributes nearly $6 billion annually to Florida's economy. The university employs about 34,000 people directly on its main campus and via UF organizations, such as the Institute of Food and Agricultural Sciences, is responsible for the creation of 74,894 jobs statewide. Unfortunately, because of the current economic environment, as of April 16*, 2009 UF is required to cut $120 million from its budget. This cut will raise local unemployment rates and will vibrate across many surrounding counties. The current proposal will create or retain 8 jobs. PUBLIC HEALTH RELEVANCE: Fatigue is a common symptom in older populations and is often associated with functional limitations, impairments and disability. Understanding the biological mechanisms underlying fatigue may help to devise novel approaches to avert fatigue and improve quality of life and independence of older adults.